Transgenerational Response of Germline Nuclear Hormone Receptor Genes to Nanoplastics at Predicted Environmental Doses in Caenorhabditis elegans

Transgenerational nanoplastic toxicity could be detected in <i>Caenorhabditis elegans</i> after exposure at the parental generation (P0-G); however, the underlying mechanisms remain largely unclear. We aimed to examine the role of germline nuclear hormone receptors (NHRs) in controlling the transgenerational toxicity of polystyrene nanoparticles (PS-NPs) based on gene expression screening and functional analysis. Among germline NHR genes, <i>daf-12</i>, <i>nhr-14</i>, and <i>nhr-47</i> expressions were increased and <i>nhr-12</i> expression was decreased by PS-NPs (1 and 10 μg/L). Transgenerational alterations in expressions of these four NHR genes were also induced by PS-NPs (1 and 10 μg/L). RNAi of <i>daf-12</i>, <i>nhr-14</i>, and <i>nhr-47</i> caused resistance, whereas RNAi of <i>nhr-12</i> conferred susceptibility to transgenerational PS-NP toxicity. After PS-NP exposure, expressions of <i>ins-3</i>, <i>daf-28</i>, and <i>ins-39</i> encoding insulin ligands, <i>efn-3</i> encoding Ephrin ligand, and <i>lin-44</i> encoding Wnt ligand, as well as expressions of their receptor genes (<i>daf-2</i>, <i>vab-1</i>, and/or <i>mig-1</i>), were dysregulated by the RNAi of <i>daf-12</i>, <i>nhr-14</i>, <i>nhr-47</i>, and <i>nhr-12</i>. Therefore, alteration in certain germline NHRs could mediate the induction of transgenerational nanoplastic toxicity by affecting secreted ligands and their receptors in the offspring of exposed organisms.